What’s cooking

We are interested in building small organic molecules and studying their functions in biological systems. Our lab started in 2004 using state-of-the-art tools to address challenging issues in the field of natural product synthesis. We focused on applying single-electron transfer and photochemistry to strategic C-C bond formation and completed the syntheses of nakiterpiosin, dibromophakellstatin, sceptrin, ageliferin, massadine, and axinellamines. We also worked on providing new transition-metal and photochemical tools to establish C-C and C-X bonds in challenging settings. We are currently building a new platform to support unorthodox catalyst development.

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Starting in 2005, we worked with Prof. Lawrence Lum who demonstrated for the first time that the Wnt pathway is druggable (Dr. Feng Cong at Novartis made the same discovery concurrently). Our lab has since been engaged in developing small-molecule porcupine (PORCN) inhibitors to suppress the secretion of Wnt proteins and tankyrase (TNKS) inhibitors to promote the degradation of β-catenin. Currently, we are using a combination of chemical and biological tools to gain a further understanding of how TNKS controls Wnt-β-catenin signaling.

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In 2012, we started to collaborate with Prof. James (Zhijian) Chen, who discovered the long-sought cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS), to develop novel immunomodulators. We helped determine the chemical structure of cGAMP, the second messenger molecule produced by cGAS, and elucidated the molecular basis for its specific recognition by stimulator of interferon genes (STING). Our joint effort has accumulated to the development of IMSA101, a cyclic dinucleotide class of investigational drug for cancer. We are also seeking to provide innovative solutions to autoimmune diseases through intervening cGAS-STING signaling.

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